vitamin-d-2 and Hypertension

Chronic kidney disease (CKD) is a common condition that has become a significant public health concern. The mainstay therapeutic approach to CKD is based on renin-angiotensin system blockade as well as blood pressure and glycemic control. Despite these interventions, the management of CKD remains suboptimal, with a large proportion of the CKD population progressing to end-stage renal disease. Newer strategies for the treatment of CKD have emerged over the past years focusing on decreasing inflammation and delaying the development of fibrosis. Despite promising results in experimental models and small randomized studies, adequately powered randomized trials are required to evaluate the benefits and risks of these therapies in the CKD population. In this review, we discuss the evidence behind, and gaps in our knowledge of, established therapies as well as newer potential strategies for managing CKD, concentrating on interventions that currently are being evaluated in randomized studies.

Topics: Allopurinol; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bicarbonates; Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Endothelin Receptor Antagonists; Ergocalciferols; Free Radical Scavengers; Glycated Hemoglobin; Gout Suppressants; Humans; Hypertension; Hyperuricemia; Hypoglycemic Agents; Kidney Failure, Chronic; Mineralocorticoid Receptor Antagonists; Pentoxifylline; Pyridoxamine; Renal Insufficiency, Chronic; Vitamin B Complex

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.

Topics: Aging; Blood Pressure; Calcitriol; Calcium; Cardiovascular Diseases; Ergocalciferols; Humans; Hypertension; Kidney Failure, Chronic; Phosphates; Receptors, Calcitriol; Vascular Calcification

Cardiovascular (CV) morbidity and mortality are significantly higher in patients with chronic kidney disease (CKD). Mineral metabolism disorders, such as hyperphosphatemia, hypocalcemia, and vitamin D deficiency, have been deeply associated not only with bone disease, but also with vascular calcification and CV disease. In addition, the decrease in vitamin D production stimulates the renin-angiotensin-aldosterone system, resulting in vasoconstriction and salt and water retention, which further promotes arterial stiffening. Several studies have shown that supplementation with vitamin D ameliorates some of these issues and is associated with improved survival. However, vitamin D also elevates serum levels of calcium and phosphorus. Selective vitamin D receptor (VDR) activators, such as paricalcitol, provide similar efficacy but are not associated with elevated serum concentrations of calcium and phosphorus. By selectively activating VDR, paricalcitol should enhance cardiorenal protection and provide significant clinical benefit. Therefore, paricalcitol may offer a novel and interesting approach to supplement and potentially enhance the standard of care in CKD patients.

Topics: Animals; Cardiovascular Diseases; Chronic Disease; Ergocalciferols; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Receptors, Calcitriol; Vitamin D Deficiency

To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS).. Single arm open label trial.. Twelve overweight and vitamin D deficient women with PCOS underwent a 2 hour oral glucose tolerance testing at baseline and following 3-month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530 mg elemental Ca daily.. Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted.. Improved serum 25OHD (p < 0.001) and reductions in total T (p = 0.036) and A (p = 0.090) levels were noted following 3-month supplementation, compared to baseline. Significant lowering in BP parameters was seen in participants with baseline BP ≥ 120/80 mmHg (n = 8) and in those with baseline serum 25OHD ≤20 ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05).. Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Calcifediol; Calcium, Dietary; Cholecalciferol; Cohort Studies; Dietary Supplements; Ergocalciferols; Female; Humans; Hyperandrogenism; Hypertension; Overweight; Patient Dropouts; Pilot Projects; Polycystic Ovary Syndrome; Testosterone Congeners; Vitamin D Deficiency; Young Adult

Vitamin D attenuates uremic cardiac hypertrophy, possibly by suppressing the myocardial renin-angiotensin system (RAS) and fibroblast growth factors (FGFs). We compared the suppression of cardiac hypertrophy and myocardial expression of RAS and FGF receptor genes offered by the vitamin D analog paricalcitol (Pc) or the angiotensin-converting enzyme inhibitor enalapril (E) in experimental uremia.. Rats with 5/6 nephrectomy received Pc or E for 8 weeks. Renal function, systolic blood pressure, and cardiac hypertrophy were evaluated. Myocardial expression of RAS genes, brain natriuretic peptide (BNP), and FGF receptor-1 (FGFR-1) were determined using quantitative reverse-transcription (pRT)-PCR.. Blood pressure, proteinuria, and serum creatinine were significantly higher in untreated uremic animals. Hypertension was significantly reduced by E but only modestly by Pc; however, cardiac hypertrophy in the untreated group was similarly attenuated by Pc or E. Upregulation of myocardial expressions of renin, angiotensinogen, FGFR-1, and BNP in untreated uremic animals was reduced similarly by Pc and E, while the angiotensin II type 1 receptor was downregulated only by E.. Uremic cardiac hypertrophy is associated with activation of the myocardial RAS and the FGFR-1. Downregulation of these genes induced by Pc and E results in similar amelioration of left ventricular hypertrophy despite the different antihypertensive effects of these drugs.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Cardiomegaly; Disease Models, Animal; Down-Regulation; Enalapril; Ergocalciferols; Fibroblast Growth Factors; Hypertension; Male; Myocardium; Nephrectomy; Rats, Sprague-Dawley; Receptor, Fibroblast Growth Factor, Type 1; Renin-Angiotensin System; RNA, Messenger; Uremia

Previous hypertension studies have shown that low levels of vitamin D are linked to elevated renin-angiotensin system. The heat shock protein 70 regulates signaling pathways for cellular oxidative stress responses. Hsp70 has been shown to protect against angiotensin II-induced hypertension and exert a cytoprotective effect. Here, we wanted to evaluate whether the vitamin D receptor (VDR) associated with Hsp70/AT1 expression may be involved in the mechanism by which paricalcitol provides renal protection in spontaneously hypertensive rats (SHRs). One-month-old female SHRs were treated for 4 months with vehicle, paricalcitol, enalapril, or a combination of both paricalcitol and enalapril. The following were determined: blood pressure; biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; and VDR, AT1 receptor, and Hsp70 expression in the renal cortex. Blood pressure was markedly reduced by enalapril or the combination but not by paricalcitol alone. However, VDR activation, enalapril or combination, prevented fibrosis, the number of TUNEL-positive apoptotic cells, mitochondrial damage, and NADPH oxidase activity in SHRs. Additionally, high AT1 receptor expression, like low Hsp70 expression (immunohistochemical/immunofluorescence studies), was reversed in the renal cortices of paricalcitol- and/or enalapril-treated animals (SHRs), and these changes were most marked in the combination therapy group. Finally, all of the recovery parameters were consistent with an improvement in VDR expression. Data suggest that Hsp70/AT1 modulated by VDR is involved in the mechanism by which paricalcitol provides renal protection in SHRs. We propose that low AT1 expression through VDR induction could be a consequence of the heat shock response Hsp70-mediated cell protection.

Topics: Animals; Antihypertensive Agents; Apoptosis; Blood Pressure; Enalapril; Ergocalciferols; Female; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Hypertension; Kidney; NADP; Protective Agents; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptors, Calcitriol

Cardiovascular diseases are the most important cause of death in patients with impaired kidney function. Left ventricular hypertrophy (LVH), cardiac interstitial fibrosis and cardiovascular calcifications are characteristic of chronic renal insufficiency (CRI). Periostin is a fibrogenesis- and calcification-related matricellular protein re-expressed in adult tissues undergoing remodelling in response to pathological stimuli. The role of periostin in CRI-induced LVH is unknown.. Rats were 5/6-nephrectomized (NX), and after 15 weeks of disease progression high-calcium, high-phosphate or paricalcitol treatment was given for 12 weeks. Cardiac tissue and blood samples were taken to study periostin gene expression and to determine factors contributing to its reactivation, respectively. Left ventricular (LV) periostin expression was also examined in response to angiotensin II or arginine(8)-vasopressin (AVP)-induced pressure overload and in spontaneously hypertensive rats.. CRI resulted in a 6.5-fold increase in LV periostin messenger RNA (mRNA) levels. Positive extracellular immunostaining for periostin was detected in areas of infiltrated inflammatory cells and fibrotic lesions. There was a significant correlation between LV periostin mRNA levels and plasma biomarkers of impaired kidney function, LVH, fibrogenesis-related proteins osteopontin and osteoactivin, and anti-calcific matrix Gla protein. Moreover, LV periostin gene expression in CRI correlated positively with systolic blood pressure (BP) and was activated rapidly in response to angiotensin II or AVP infusions.. Periostin is involved in fibrotic cardiac remodelling in CRI. The re-expression of periostin is localized to the fibrotic and inflammatory lesions and is most likely the consequence of elevated BP.

Topics: Animals; Biomarkers; Blotting, Western; Bone Density Conservation Agents; Calcinosis; Cell Adhesion Molecules; Disease Models, Animal; Ergocalciferols; Fibrosis; Gene Expression; Heart Ventricles; Hypertension; Immunoenzyme Techniques; Kidney Function Tests; Myocardial Infarction; Nephrectomy; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Renal Insufficiency; RNA, Messenger

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Dietary Supplements; Ergocalciferols; Female; Humans; Hypertension; Kidney Diseases; Male; Parathyroid Hormone; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Treatment Outcome

Topics: Animals; Aorta, Thoracic; Cholesterol; Ergocalciferols; Hypertension; Microscopy, Electron; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR

Topics: Animals; Arteritis; Cholesterol, Dietary; Ergocalciferols; Hypertension; Mesenteric Arteries; Microscopy, Electron; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR

Plasma 25-OH-D levels of normotensive and hypertensive subjects living in a highly industrial and in a nonindustrial area, were estimated. Significantly higher values were found in normotensive subjects than in hypertensive patients. Severity of arterial hypertension was not related to plasma 25-OH-D. Both groups of subjects (normotensive and hypertensive) living in the industrial area with high air pollution had lower 25-OH-D concentrations than those living in the nonindustrial region. Data presented in this paper suggest that antihypertensive treatment by pharmacologic agents exerts a depressive effect on plasma 25-OH-D level.

Topics: 25-Hydroxyvitamin D 2; Adult; Air Pollutants; Alkaline Phosphatase; Calcium; Ergocalciferols; Female; Humans; Hydrochlorothiazide; Hypertension; Industry; Male; Middle Aged; Phosphates

1. Hypertension was produced in rabbits by unilateral renal encapsulation combined with contralateral nephrectomy or by the administration of calciferol and calcium lactate. 2. Weighed post mortem, the adrenal glands from the two hypertensive groups were significantly heavier than those from normotensive animals of similar weight. There was a direct correlation between the adrenal gland weight and the mean arterial blood pressure measured at the time of the terminal experiment. 3. The catecholamine content of the adrenal glands from the two groups of hypertensive animals was similar to that of the normotensive animals. 4. There was histological evidence of adrenal cortical hypertrophy in the glands of the hypertensive groups of animals.

Topics: Adrenal Glands; Animals; Blood Pressure; Body Weight; Catecholamines; Ergocalciferols; Female; Hypertension; Hypertension, Renal; Kidney; Male; Nephrectomy; Organ Size; Rabbits

Topics: Animals; Aorta; Calcinosis; Ergocalciferols; Hypertension; Pressoreceptors; Rabbits

Topics: Alcohols; Animals; Arteriosclerosis; Blood Pressure Determination; Ergocalciferols; Hypertension; Male; Mycobacterium bovis; Mycobacterium tuberculosis; Rats; Toluene; Tuberculin

Topics: Chlorides; Citrates; Diet; Ergocalciferols; Hypertension; Magnesium; Mental Disorders; Pharmacology; Rats; Research; Stress, Physiological; Toxicology

Topics: Brain; Cardiovascular Diseases; Cerebral Hemorrhage; Chlorides; Cholesterol; Dietary Fats; Dietary Proteins; Ergocalciferols; Hypercholesterolemia; Hypertension; Hypokalemia; Magnesium Deficiency; Pathology; Potassium Deficiency; Rats; Research; Sodium

Topics: Blood Pressure; Calcium, Dietary; Cholesterol; Cold Temperature; Diet; Diet, Atherogenic; Dietary Fats; Electrolytes; Ergocalciferols; Hypertension; Lipid Metabolism; Magnesium; Metabolism; Myocardial Infarction; Rats; Reflex; Research; Sodium

Topics: Arteriosclerosis; Bacterial Proteins; Ergocalciferols; Hypertension; Mycobacterium bovis; Mycobacterium tuberculosis; Pharmacology; Rats; Research; Toxicology; Vitamins

Topics: Child; Drug-Related Side Effects and Adverse Reactions; Ergocalciferols; Humans; Hypercalcemia; Hypertension; Kidney Function Tests; Poisoning; Toxicology

Topics: Angina Pectoris; Blood Chemical Analysis; Cholesterol; Chromatography; Drug Therapy; Ergocalciferols; Hypertension; Sterols; Triparanol

Topics: Abortion, Induced; Abortion, Spontaneous; Abortion, Therapeutic; Ergocalciferols; Female; Humans; Hypertension; Hypertension, Renal; Kidney; Poisoning; Pregnancy; Toxicology